The proposed studies are designed to investigate absorptive and secretory phenomena in the human intestine that are relevant to the understanding of normal physiology and disease states. It is now recognized that the function of the human intestine is in part under the control of a variety of gastrointestinal hormones, many of which are present in both the brain and the gut. In these studies we first plan to investigate the effect of polypeptides and related compounds on water and solute movement in the human intestine. We will use steady-state intestinal perfusion methods and intravenous infusion of such agents as vasoactive intestinal polypeptide (VIP), motilin, somatostatin and serotonin to characterize their effect on absorption and secretion in healthy subjects. This information will help to understand the pathophysiology of diseases that are associated with disturbed production or release of these agents into the circulation (e.g., pancreatic cholera syndrome). Second, we will use VIP, which we have already described as being capable of inducing active chloride secretion in the jejunum, as a secretory model in man in order to identify inhibitors of intestinal secretion. Identifying such inhibitors may be of immediate clinical importance in various forms of secretory diarrhea, particularly in the pancreatic cholera syndrome. Third, we plan to directly study patients with chronic large-volume diarrhea and we will investigate the role of intestinal secretogogues in their condition. Patients with polypeptide producing tumors will also be studied to better characterize the gastrointestinal manifestations of these diseases. Taken together, these studies will provide new information on the function of the intestine with respect to water and solute movement in health and disease and clarify the role of polypeptide hormones and related compounds under these circumstances.